Senfl probably grew up in Zürich, and at about age 10 he joined Holy Roman Emperor Maximilian I’s Hofkapelle choir. He is thought to have entered the priesthood after his voice changed, an option generally given to pubescent choirboys, and thus studied briefly on his own in Vienna, but otherwise he stayed mostly with the Kapelle. A pupil of Heinrich Isaac, Senfl rapidly mastered composition in the Franco-Flemish style. He collaborated with his teacher as a copyist and became chamber composer to the Holy Roman emperor Maximilian IMaximilian after Isaac’s death in 1517. About 1520 that time he moved to Augsburg, where he completed Isaac’s Choralis Constantinus and edited the Liber selectarum cantionum (1520), one of the earliest examples of German printed music. From 1523 he worked in Munich. Senfl’s seven masses also started to gain international recognition for his scholarly interests in musical rhythm and poetic metre. After the emperor’s death in 1519, Senfl tried without success to become a musician to Maximilian’s successor, Charles V. Failing to win favour with Charles and having much difficulty receiving the payment or recognition he had been promised during Maximilian’s reign, Senfl embarked on a a period of extensive travel in the early 1520s. In 1523 he settled in Munich, having obtained a post in the Hofkapelle of Duke William IV of Bavaria. He left the religious order in 1529 and took a wife, and by the following year he had begun corresponding with religious reformer Martin Luther, for whom he wrote two motets. Despite Senfl’s popularity as a composer, little is known of his later life, including the date of his death.

Among Senfl’s works are seven masses, which employ parody (reworking of a preexistent part-song) and cantus firmus; one mass combines two preexisting melodies simultaneously. He published about 150 also composed hundreds of motets and German lieder(1534, 1544), completed Isaac’s Choralis Constantinus (published posthumously, 1550–55), and edited the Liber selectarum cantionum (1520), one of the earliest examples of German printed music.